Regulation of spontaneous inhibitory synaptic transmission by endogenous glutamate via non-NMDA receptors in cultured rat hippocampal neurons
Regulation of spontaneous inhibitory synaptic transmission by endogenous glutamate via non-NMDA receptors in cultured rat hippocampal neurons
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DOI：
10.1016/s0028-3908(00)00213-6
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发表时间：
2001-05-01
影响因子：
4.7
通讯作者：
Vignes, M
中科院分区：
文献类型：
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作者：
Vignes, M
在培养的大鼠海马神经元中研究了内源性谷氨酸对γ -氨基丁酸（GABA）介导的自发性抑制性突触传递的调节。体外培养7 d (DIV)，可检测到自发兴奋性突触后电流（sEPSCs）和自发抑制性突触后电流（sIPSCs）。15 DIV后，在-30 mV保持电压下记录，大多数突触后自发电流以sEPSC/sIPSC序列出现。在谷氨酸α -氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体亚型拮抗剂LY303070的存在下，sIPSC的频率和幅度均强烈且可逆地降低。n -甲基- d -天冬氨酸（NMDA）受体拮抗剂2-氨基-5-磷酸戊酸（AP5）对sIPSC无明显影响，而环噻嗪可显著增加sIPSC的发生频率。在AMPA受体阻断下，kainate-和glur5选择性kainate受体激动剂(RS)-2-氨基-3-（3-羟基-5-叔丁基异恶唑-4-基）propanoic acid （ATPA）和(S)-5-iodowillardiine （5will）诱导小振幅sIPSC的频率大幅增强，而非nmda受体拮抗剂2,3-二氢-6-硝基-7-磺胺酰基苯并喹啉（NBQX）阻断了sIPSC的频率。这些效应均对河豚毒素（TTX）敏感。在LY303070和TTX存在的情况下，kainate可以诱导小的内向电流，而GluR5激动剂则没有作用。在NMDA和AMPA受体拮抗剂存在的情况下，谷氨酸摄取抑制剂l -反式吡咯烷-2-4-二羧酸（t-PDC）可以恢复sIPSC。当NBQX作为AMPA拮抗剂时，t-PDC的刺激作用被阻断，而I组代谢型谷氨酸激动剂3.5-二羟基苯基甘氨酸（DHPG）则诱导sIPSC的强烈增强。因此，AMPA和kainate受体都可以调节培养海马神经元的抑制性突触传递，前者通过强直激活，后者通过损害谷氨酸摄取而增加谷氨酸浓度。2001爱思唯尔科学有限公司版权所有。
The regulation of gamma -aminobutyric acid (GABA)-mediated spontaneous inhibitory synaptic transmission by endogenously released glutamate was studied in cultured rat hippocampal neurons. After 7 days in vitro (DIV), both spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) could be detected. After 15 DIV, most postsynaptic spontaneous currents occurred as sEPSC/sIPSC sequences when recorded at a holding voltage of -30 mV. In the presence of the glutamate alpha -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtype antagonist LY303070, both the frequency and amplitude of sIPSC were strongly and reversibly reduced. The N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5), had no effect on sIPSC while cyclothiazide strongly increased sIPSC frequency. Under blockade of AMPA receptors, the kainate- and GluR5-selective kainate receptor agonists, (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid) (ATPA) and (S)-5-iodowillardiine (5IWill), induced a large enhancement of the Frequency of small-amplitude sIPSC which was blocked by the non-NMDA receptor antagonist, 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(qunioxaline (NBQX). All of these effects were sensitive to tetrodotoxin (TTX). In the presence of LY303070 and TTX, kainate could induce a small inward current while GluR5 agonists had no effect. In the presence of NMDA and AMPA receptor antagonists, the glutamate uptake inhibitor L-trans-pyrrolidine-2-4-dicarboxylic acid (t-PDC) could restore sIPSC. When NBQX was used as an AMPA antagonist, the stimulatory effect of t-PDC was blocked while the group I metabotropic glutamate agonist, 3.5-dihydroxyphenylglycine (DHPG), induced a strong enhancement of sIPSC. Therefore, both AMPA and kainate receptors can regulate inhibitory synaptic transmission in cultured hippocampal neurons, the former by tonic activation, the latter when the glutamate concentration is increased by impairing glutonate uptake. (C) 2001 Elsevier Science Ltd. All rights reserved.